TABLE 2.

Inflammatory models for the study of visceral pain

Animal	Inflammatory agents	Injection site	Purpose of the study	Findings	References
Rat	TNBS in 50% ethanol	Colon	To develop a simple and reproducible model of chronic colonic inflammation by the intraluminal instillation of a solution containing a barrier breaker and a hapten	The combined administration of TNBS and ethanol resulted in the development of severe, transmural, granulomatous inflammation of the distal colon which may be useful for the study of the etiopathogenesis of chronic intestinal inflammation as well as providing an inexpensive model suitable for assessing potential treatments	Morris et al 87
Rat	Dibutyltin dichloride, 10% ethanol	Tail vein injection, orally	Nociception in persistent pancreatitis and responsivity of Morphine	Animals with the dibutyltin dichloride‐induced experimental pancreatitis expressed serum, histologic, and behavioral characteristics similar in duration to those present during acute attacks experienced by patients with chronic pancreatitis and pain‐related measures were found to be abrogated by morphine	Vera‐Portocarrero et al 13
Female rat	0.2% acetic acid	Intravesicular	To determine in female rats whether abdominal muscle discharges during normal voiding and to describe the effect of bladder irritation on this visceromotor activity	Acetic acid infusion reduced the inter contraction interval and increased bladder contraction duration. The afferents activating the visceromotor reflex during normal voiding and the increased reflex in response to acetic acid are probably both carried by the pelvic nerve. Abdominal muscle activity induced by bladder distension has been considered to be a pain marker	Cruz and Downie 77
Mice	Zymosan	Colon	Examination of contributions of 2 proteins, TRPV1 and ASIC3, on development of behavioral hypersensitivity and assessment of the function of colon mechanoreceptors of hypersensitive mice	Zymosan sensitized the colonic mechanoreceptors acutely in vitro and chronic behavioral hypersensitivity (≥7 wk) in the quiescent inflammation. TRPV1 and ASIC3 proteins may be important peripheral mediators for development of functional visceral hypersensitivity	Jones et al 8
Mice	Acrolein	Intravesicular	Evaluation of the severity of cystitis in response to increasing doses of acrolein through direct intravesicular administration	Intravesical instillation of acrolein produces dose‐dependent cystitis	Bjorling et al 78
Guinea pig	TNBS	Ileal lumen	Morphological and functional changes in neurons projecting to the ileal mucosa at the early stage after inflammatory damage	Inflammation may be an important contributing factor to the neuronal hyperexcitability at the acute stage of inflammation	Nurgali et al 76

Animals	Inflammatory agents	Injection site/stimuli	Purpose of the study	Findings	References
Wild mice	Intraluminal distension (100‐120 mmHg)	Colorectal	To identify the extrinsic nerve pathway(s) underlies nociception from the colorectum to the spinal cord of rodents	The visceral pain pathway activated by acute noxious distension of the terminal 15 mm of mouse colorectum is transmitted predominantly, if not solely, through rectal/pelvic afferent nerve fibers to the spinal cord. The sensory neurons of this spinal afferent pathway lie primarily in the lumbosacral region of the spinal cord, between L6 and S1	Kyloh et al 88
Male rat	Balloon	Colon	Balloon distension of colon to investigate nonsteroidal anti‐inflammatory drug's effectiveness in CRD‐induced visceral pain model	Metamizole, dexketoprofen and meloxicam show antinociceptive effect with different duration of action on CRD‐induced visceral pain model	Baskın et al 89
Rat	Intra‐colonic infusion of 0.5% acetic acid	Intra‐colonic	To investigate whether NO‐ mediated colonic motility was altered in rat IBS model, using different forms of NO‐synthase (NOS) inhibitors	The mean pressure values of spontaneous contractions and KCL (80 mmol/L) responses of distal colonic segments were similar in normal and IBS rats. L‐NAME and ARL‐17477 significantly increased the mean pressure of spontaneous colonic contractions in normal rats versus own base values (P < .05), but this increase did not significantly different when compared to IBS rats	Temiz et al 90
Rat	TNBS	Ileum	Investigation of the visceral hypersensitivity provoked by TNBS‐induced ileitis rats	Transmural ileitis including granuloma and VH	Shah et al 10
Rat	0.5% acetic acid	Intra‐colonic	To investigate in vitro effects of varenicline on spontaneous contractile responses of proximal and distal colon smooth muscle in control and IBS rats	Varenicline significantly decreased the mean pressure of spontaneous colonic contractions in both control and IBS rats compared to their baseline values in only distal colon (P < .05). The relaxation responses of distal colons were not significantly different between IBS and control groups (P > .05)	Kaya Temiz et al 91
Goat	TNBS	Ileum	To testify the effect of electroacupuncture (EA) on ileitis‐provoked VH, and to confirm whether EA attenuates VH through JAK2/STAT3) signaling pathway in the PAG‐RVM‐SDH axis	EA attenuates VH probably through inhibiting JAK2/STAT3 signaling pathway in the PAG‐RVM‐SDH axis	Wan et al 7

Abbreviations: ASIC3, Acid sensing ion channel‐3; CRD, Colorectal Distension; EMG, electromyography; IBD, inflammatory bowel disease; IBS, irritable bowel syndrome; IL‐1β, Interleukin‐1 beta; IL‐6, Interleukin‐6; JAK, Janus Kinase; NO, Nitric Oxide; PAG, periaqueductal gray; RVM, rostral ventromedial medulla; SDH, spinal dorsal horn; STAT, signal transducers and activators of transcription; TNBS, 2,4,6‐trinitrobenzene sulfonic acid; TNFα, Tumor Necrosis Factor‐alpha; TRPV1, Transient Receptor Potential Vanilloid Type 1; UBD, urinary bladder distention; VH, visceral hypersensitivity.